WO2009152372A1 - Contrôle de la physiologie des vaisseaux sanguins pour le traitement de troubles cutanés - Google Patents
Contrôle de la physiologie des vaisseaux sanguins pour le traitement de troubles cutanés Download PDFInfo
- Publication number
- WO2009152372A1 WO2009152372A1 PCT/US2009/047098 US2009047098W WO2009152372A1 WO 2009152372 A1 WO2009152372 A1 WO 2009152372A1 US 2009047098 W US2009047098 W US 2009047098W WO 2009152372 A1 WO2009152372 A1 WO 2009152372A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vasodilation
- blood vessel
- composition
- skin
- abnormal blood
- Prior art date
Links
- 210000004204 blood vessel Anatomy 0.000 title claims abstract description 116
- 208000017520 skin disease Diseases 0.000 title claims abstract description 29
- 230000035479 physiological effects, processes and functions Effects 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 110
- 238000000034 method Methods 0.000 claims abstract description 64
- 230000024883 vasodilation Effects 0.000 claims abstract description 64
- 230000002159 abnormal effect Effects 0.000 claims abstract description 46
- 208000028867 ischemia Diseases 0.000 claims abstract description 29
- 206010047139 Vasoconstriction Diseases 0.000 claims abstract description 21
- 230000025033 vasoconstriction Effects 0.000 claims abstract description 21
- 230000001939 inductive effect Effects 0.000 claims abstract description 14
- 230000001747 exhibiting effect Effects 0.000 claims abstract description 6
- 238000011282 treatment Methods 0.000 claims description 59
- 238000009472 formulation Methods 0.000 claims description 27
- 201000004700 rosacea Diseases 0.000 claims description 22
- 241001303601 Rosacea Species 0.000 claims description 20
- 230000000699 topical effect Effects 0.000 claims description 18
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- 208000009056 telangiectasis Diseases 0.000 claims description 10
- -1 phenyl epinephrine Chemical compound 0.000 claims description 9
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 claims description 8
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 8
- 229960000458 allantoin Drugs 0.000 claims description 8
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 8
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 claims description 8
- 229940100555 2-methyl-4-isothiazolin-3-one Drugs 0.000 claims description 7
- 230000005670 electromagnetic radiation Effects 0.000 claims description 7
- 235000011187 glycerol Nutrition 0.000 claims description 7
- 229960005150 glycerol Drugs 0.000 claims description 7
- BEGLCMHJXHIJLR-UHFFFAOYSA-N methylisothiazolinone Chemical compound CN1SC=CC1=O BEGLCMHJXHIJLR-UHFFFAOYSA-N 0.000 claims description 7
- 244000126155 Lycopus uniflorus Species 0.000 claims description 6
- 235000002280 Lycopus uniflorus Nutrition 0.000 claims description 6
- 206010043189 Telangiectasia Diseases 0.000 claims description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 6
- JIVZKJJQOZQXQB-UHFFFAOYSA-N tolazoline Chemical compound C=1C=CC=CC=1CC1=NCCN1 JIVZKJJQOZQXQB-UHFFFAOYSA-N 0.000 claims description 6
- 229960002312 tolazoline Drugs 0.000 claims description 6
- 231100000216 vascular lesion Toxicity 0.000 claims description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
- 239000004202 carbamide Substances 0.000 claims description 5
- 229920006037 cross link polymer Polymers 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000002604 ultrasonography Methods 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 244000144927 Aloe barbadensis Species 0.000 claims description 4
- 235000002961 Aloe barbadensis Nutrition 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims description 4
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 claims description 4
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 4
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 206010057041 Poikiloderma Diseases 0.000 claims description 4
- 235000008737 Polygonatum biflorum Nutrition 0.000 claims description 4
- 235000004506 Polygonatum multiflorum Nutrition 0.000 claims description 4
- 244000294611 Punica granatum Species 0.000 claims description 4
- 235000014360 Punica granatum Nutrition 0.000 claims description 4
- 240000000353 Ruscus aculeatus Species 0.000 claims description 4
- 235000003500 Ruscus aculeatus Nutrition 0.000 claims description 4
- 206010046996 Varicose vein Diseases 0.000 claims description 4
- 208000009443 Vascular Malformations Diseases 0.000 claims description 4
- 125000005250 alkyl acrylate group Chemical group 0.000 claims description 4
- 235000011399 aloe vera Nutrition 0.000 claims description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- 229960003121 arginine Drugs 0.000 claims description 4
- 229960003589 arginine hydrochloride Drugs 0.000 claims description 4
- 229940089116 arnica extract Drugs 0.000 claims description 4
- 235000013877 carbamide Nutrition 0.000 claims description 4
- 229960000541 cetyl alcohol Drugs 0.000 claims description 4
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 4
- 229940075529 glyceryl stearate Drugs 0.000 claims description 4
- 239000010651 grapefruit oil Substances 0.000 claims description 4
- 201000011066 hemangioma Diseases 0.000 claims description 4
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 4
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 4
- 229960001238 methylnicotinate Drugs 0.000 claims description 4
- 229940084047 nymphaea alba flower extract Drugs 0.000 claims description 4
- 229940100460 peg-100 stearate Drugs 0.000 claims description 4
- 229940045871 sodium palmitoyl proline Drugs 0.000 claims description 4
- GJIFNLAZXVYJDI-FYZYNONXSA-M sodium;(2s)-1-hexadecanoylpyrrolidine-2-carboxylate Chemical compound [Na+].CCCCCCCCCCCCCCCC(=O)N1CCC[C@H]1C([O-])=O GJIFNLAZXVYJDI-FYZYNONXSA-M 0.000 claims description 4
- 229940045136 urea Drugs 0.000 claims description 4
- 208000027185 varicose disease Diseases 0.000 claims description 4
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 3
- 229960001948 caffeine Drugs 0.000 claims description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 3
- 229940086555 cyclomethicone Drugs 0.000 claims description 3
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229960005139 epinephrine Drugs 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000003921 oil Substances 0.000 claims description 3
- 229940060184 oil ingredients Drugs 0.000 claims description 3
- 229940083618 sodium nitroprusside Drugs 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- 229960004274 stearic acid Drugs 0.000 claims description 3
- 229930182837 (R)-adrenaline Natural products 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 230000009089 cytolysis Effects 0.000 claims description 2
- 229910052743 krypton Inorganic materials 0.000 claims description 2
- 239000004065 semiconductor Substances 0.000 claims description 2
- 244000301850 Cupressus sempervirens Species 0.000 claims 1
- 240000005166 Polygonatum biflorum Species 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000035876 healing Effects 0.000 abstract description 6
- 210000003491 skin Anatomy 0.000 description 42
- 239000005526 vasoconstrictor agent Substances 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 21
- 239000003071 vasodilator agent Substances 0.000 description 16
- 229940124549 vasodilator Drugs 0.000 description 14
- 230000001815 facial effect Effects 0.000 description 10
- 230000008901 benefit Effects 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000010339 dilation Effects 0.000 description 6
- 239000012049 topical pharmaceutical composition Substances 0.000 description 6
- 230000017531 blood circulation Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 238000011010 flushing procedure Methods 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000035515 penetration Effects 0.000 description 5
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 4
- 229930064664 L-arginine Natural products 0.000 description 4
- 235000014852 L-arginine Nutrition 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 238000010336 energy treatment Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 230000000302 ischemic effect Effects 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 241000218691 Cupressaceae Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 241000756042 Polygonatum Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000008451 emotion Effects 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 206010047141 Vasodilatation Diseases 0.000 description 2
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229960004042 diazoxide Drugs 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960002474 hydralazine Drugs 0.000 description 2
- 230000004047 hyperresponsiveness Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000005414 inactive ingredient Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 229940124583 pain medication Drugs 0.000 description 2
- MRWQRJMESRRJJB-UHFFFAOYSA-N pentifylline Chemical compound O=C1N(CCCCCC)C(=O)N(C)C2=C1N(C)C=N2 MRWQRJMESRRJJB-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 230000036561 sun exposure Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- BFCDFTHTSVTWOG-YLJYHZDGSA-N (1S,2R)-2-(octylamino)-1-[4-(propan-2-ylthio)phenyl]-1-propanol Chemical compound CCCCCCCCN[C@H](C)[C@@H](O)C1=CC=C(SC(C)C)C=C1 BFCDFTHTSVTWOG-YLJYHZDGSA-N 0.000 description 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- XSTJTOKYCAJVMJ-GVTSEVKNSA-N (z)-but-2-enedioic acid;(e)-1-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one Chemical compound OC(=O)\C=C/C(O)=O.COC1=C(OC)C(OC)=CC(\C=C\C(=O)N2CCN(CC(=O)N3CCCC3)CC2)=C1 XSTJTOKYCAJVMJ-GVTSEVKNSA-N 0.000 description 1
- ZDPACSAHMZADFZ-UHFFFAOYSA-N 1-[3-(2,4,6-Trimethoxybenzoyl)propyl]pyrrolidinium chloride Chemical compound [Cl-].COC1=CC(OC)=CC(OC)=C1C(=O)CCC[NH+]1CCCC1 ZDPACSAHMZADFZ-UHFFFAOYSA-N 0.000 description 1
- NLDJGIDWOVFPSS-UHFFFAOYSA-N 2-(1,3-dimethyl-2,6-dioxopurin-7-yl)acetic acid;4-[1-hydroxy-2-(1-phenoxypropan-2-ylamino)propyl]phenol Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)=O)C=N2.C=1C=C(O)C=CC=1C(O)C(C)NC(C)COC1=CC=CC=C1 NLDJGIDWOVFPSS-UHFFFAOYSA-N 0.000 description 1
- OTCQHDHPGKBMGU-UHFFFAOYSA-N 2-(2,5-dioxopyrrolidin-1-yl)ethyl prop-2-enoate Chemical compound C=CC(=O)OCCN1C(=O)CCC1=O OTCQHDHPGKBMGU-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- NKQVYJRZBVRXRU-UHFFFAOYSA-N 2-methyl-2-(methylamino)propanenitrile Chemical compound CNC(C)(C)C#N NKQVYJRZBVRXRU-UHFFFAOYSA-N 0.000 description 1
- JXZZEXZZKAWDSP-UHFFFAOYSA-N 3-(2-(4-Benzamidopiperid-1-yl)ethyl)indole Chemical compound C1CN(CCC=2C3=CC=CC=C3NC=2)CCC1NC(=O)C1=CC=CC=C1 JXZZEXZZKAWDSP-UHFFFAOYSA-N 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 1
- QESTYTNSJJTQCI-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]benzene-1,2-diol Chemical compound COC1=CC=CC=C1N1CCN(CC(O)C=2C=C(O)C(O)=CC=2)CC1 QESTYTNSJJTQCI-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- GEPMAHVDJHFBJI-UHFFFAOYSA-N 7-[2-hydroxy-3-[2-hydroxyethyl(methyl)amino]propyl]-1,3-dimethylpurine-2,6-dione;pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1.CN1C(=O)N(C)C(=O)C2=C1N=CN2CC(O)CN(CCO)C GEPMAHVDJHFBJI-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 101100310593 Candida albicans (strain SC5314 / ATCC MYA-2876) SOD4 gene Proteins 0.000 description 1
- 206010007191 Capillary fragility Diseases 0.000 description 1
- 206010008570 Chloasma Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- VPAXJOUATWLOPR-UHFFFAOYSA-N Conferone Chemical compound C1=CC(=O)OC2=CC(OCC3C4(C)CCC(=O)C(C)(C)C4CC=C3C)=CC=C21 VPAXJOUATWLOPR-UHFFFAOYSA-N 0.000 description 1
- 235000013175 Crataegus laevigata Nutrition 0.000 description 1
- 240000001879 Digitalis lutea Species 0.000 description 1
- ILKBHIBYKSHTKQ-UHFFFAOYSA-N Diisopropylamine dichloroacetate Chemical compound OC(=O)C(Cl)Cl.CC(C)NC(C)C ILKBHIBYKSHTKQ-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- GUIBJJJLGSYNKE-UHFFFAOYSA-N Hepronicate Chemical compound C=1C=CN=CC=1C(=O)OCC(COC(=O)C=1C=NC=CC=1)(CCCCCC)COC(=O)C1=CC=CN=C1 GUIBJJJLGSYNKE-UHFFFAOYSA-N 0.000 description 1
- DMPRDSPPYMZQBT-CEAXSRTFSA-N Ifenprodil tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1.C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 DMPRDSPPYMZQBT-CEAXSRTFSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- KUEUWHJGRZKESU-UHFFFAOYSA-N Niceritrol Chemical compound C=1C=CN=CC=1C(=O)OCC(COC(=O)C=1C=NC=CC=1)(COC(=O)C=1C=NC=CC=1)COC(=O)C1=CC=CN=C1 KUEUWHJGRZKESU-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- CLJHABUMMDMAFA-UHFFFAOYSA-N Nylidrin hydrochloride Chemical compound [Cl-].C=1C=C(O)C=CC=1C(O)C(C)[NH2+]C(C)CCC1=CC=CC=C1 CLJHABUMMDMAFA-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 108010064719 Oxyhemoglobins Proteins 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- 239000000026 Pentaerythritol tetranitrate Substances 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 description 1
- RBQOQRRFDPXAGN-UHFFFAOYSA-N Propentofylline Chemical compound CN1C(=O)N(CCCCC(C)=O)C(=O)C2=C1N=CN2CCC RBQOQRRFDPXAGN-UHFFFAOYSA-N 0.000 description 1
- MYHXHCUNDDAEOZ-UHFFFAOYSA-N Prostaglandin A&2% Natural products CCCCCC(O)C=CC1C=CC(=O)C1CC=CCCCC(O)=O MYHXHCUNDDAEOZ-UHFFFAOYSA-N 0.000 description 1
- 101100190148 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PGA2 gene Proteins 0.000 description 1
- 108010083387 Saralasin Proteins 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- 208000026349 Vascular skin disease Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- VRYMTAVOXVTQEF-UHFFFAOYSA-N acetic acid [4-[2-(dimethylamino)ethoxy]-2-methyl-5-propan-2-ylphenyl] ester Chemical compound CC(C)C1=CC(OC(C)=O)=C(C)C=C1OCCN(C)C VRYMTAVOXVTQEF-UHFFFAOYSA-N 0.000 description 1
- 239000003043 adrenergic neuron blocking agent Substances 0.000 description 1
- GRTOGORTSDXSFK-XJTZBENFSA-N ajmalicine Chemical compound C1=CC=C2C(CCN3C[C@@H]4[C@H](C)OC=C([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 GRTOGORTSDXSFK-XJTZBENFSA-N 0.000 description 1
- 102000015007 alpha-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006816 alpha-adrenergic receptor activity proteins Proteins 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000003501 anti-edematous effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 1
- PARMADWNFXEEFC-UHFFFAOYSA-N bamethan sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[NH2+]CC(O)C1=CC=C(O)C=C1.CCCC[NH2+]CC(O)C1=CC=C(O)C=C1 PARMADWNFXEEFC-UHFFFAOYSA-N 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 229960003902 bencyclane fumarate Drugs 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- 229960004980 betanidine Drugs 0.000 description 1
- NIVZHWNOUVJHKV-UHFFFAOYSA-N bethanidine Chemical compound CN\C(=N/C)NCC1=CC=CC=C1 NIVZHWNOUVJHKV-UHFFFAOYSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 229960002113 buflomedil hydrochloride Drugs 0.000 description 1
- 229960003756 butalamine Drugs 0.000 description 1
- VYWQZAARVNRSTR-UHFFFAOYSA-N butalamine Chemical compound O1C(NCCN(CCCC)CCCC)=NC(C=2C=CC=CC=2)=N1 VYWQZAARVNRSTR-UHFFFAOYSA-N 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 229960003025 ciclonicate Drugs 0.000 description 1
- GQSGZTBDVNUIQS-DGCLKSJQSA-N ciclonicate Chemical compound C1C(C)(C)C[C@H](C)C[C@H]1OC(=O)C1=CC=CN=C1 GQSGZTBDVNUIQS-DGCLKSJQSA-N 0.000 description 1
- 229960005025 cilazapril Drugs 0.000 description 1
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
- 229960004201 cinepazide Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 230000001427 coherent effect Effects 0.000 description 1
- JECGPMYZUFFYJW-UHFFFAOYSA-N conferone Natural products CC1=CCC2C(C)(C)C(=O)CCC2(C)C1COc3cccc4C=CC(=O)Oc34 JECGPMYZUFFYJW-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000729 cyclandelate Drugs 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- JWPGJSVJDAJRLW-UHFFFAOYSA-N debrisoquin Chemical compound C1=CC=C2CN(C(=N)N)CCC2=C1 JWPGJSVJDAJRLW-UHFFFAOYSA-N 0.000 description 1
- 229960004096 debrisoquine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- WSDISUOETYTPRL-UHFFFAOYSA-N dmdm hydantoin Chemical compound CC1(C)N(CO)C(=O)N(CO)C1=O WSDISUOETYTPRL-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229940064982 ethylnicotinate Drugs 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000003457 ganglion blocking agent Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000020708 ginger extract Nutrition 0.000 description 1
- 229940002508 ginger extract Drugs 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 229960003602 guanethidine Drugs 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229950000262 hepronicate Drugs 0.000 description 1
- RVYGVBZGSFLJKH-UHFFFAOYSA-N hexyl pyridine-3-carboxylate Chemical compound CCCCCCOC(=O)C1=CC=CN=C1 RVYGVBZGSFLJKH-UHFFFAOYSA-N 0.000 description 1
- 229940051295 hexylnicotinate Drugs 0.000 description 1
- 229960000204 ifenprodil tartrate Drugs 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 229960002056 indoramin Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229960005436 inositol nicotinate Drugs 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 229960000201 isosorbide dinitrate Drugs 0.000 description 1
- 229960004164 isoxsuprine hydrochloride Drugs 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- 229960003709 kallidinogenase Drugs 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960003632 minoxidil Drugs 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- MFZCIDXOLLEMOO-GYSGTQPESA-N myo-inositol hexanicotinate Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](OC(=O)C=2C=NC=CC=2)[C@@H](OC(=O)C=2C=NC=CC=2)[C@@H]1OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)C(=O)C1=CC=CN=C1 MFZCIDXOLLEMOO-GYSGTQPESA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- JVWOCHRRAWHKLT-UHFFFAOYSA-N nicametate Chemical compound CCN(CC)CCOC(=O)C1=CC=CN=C1 JVWOCHRRAWHKLT-UHFFFAOYSA-N 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229960000827 niceritrol Drugs 0.000 description 1
- 229960004552 nicofuranose Drugs 0.000 description 1
- FUWFSXZKBMCSKF-ZASNTINBSA-N nicofuranose Chemical compound C([C@]1(O)[C@H]([C@H](OC(=O)C=2C=NC=CC=2)[C@@H](COC(=O)C=2C=NC=CC=2)O1)OC(=O)C=1C=NC=CC=1)OC(=O)C1=CC=CN=C1 FUWFSXZKBMCSKF-ZASNTINBSA-N 0.000 description 1
- 229960004738 nicotinyl alcohol Drugs 0.000 description 1
- 229960000839 nicotinyl alcohol tartrate Drugs 0.000 description 1
- NPORIZAYKBQYLF-LREBCSMRSA-N nicotinyl alcohol tartrate Chemical compound OCC1=CC=CN=C1.OC(=O)[C@H](O)[C@@H](O)C(O)=O NPORIZAYKBQYLF-LREBCSMRSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229960002460 nitroprusside Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000037325 pain tolerance Effects 0.000 description 1
- 230000001354 painful effect Effects 0.000 description 1
- MXQKCNCLQIHHJA-UHFFFAOYSA-N papaveroline Chemical compound C1=C(O)C(O)=CC=C1CC1=NC=CC2=CC(O)=C(O)C=C12 MXQKCNCLQIHHJA-UHFFFAOYSA-N 0.000 description 1
- 229950005542 papaveroline Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960004321 pentaerithrityl tetranitrate Drugs 0.000 description 1
- 229960002371 pentifylline Drugs 0.000 description 1
- HSMKTIKKPMTUQH-WBPXWQEISA-L pentolinium tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O.OC(=O)[C@H](O)[C@@H](O)C([O-])=O.C1CCC[N+]1(C)CCCCC[N+]1(C)CCCC1 HSMKTIKKPMTUQH-WBPXWQEISA-L 0.000 description 1
- 229950008637 pentolonium Drugs 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229960003418 phenoxybenzamine Drugs 0.000 description 1
- 229960001999 phentolamine Drugs 0.000 description 1
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
- 229950011542 pipratecol Drugs 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 229960002934 propentofylline Drugs 0.000 description 1
- MYHXHCUNDDAEOZ-FOSBLDSVSA-N prostaglandin A2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1C=CC(=O)[C@@H]1C\C=C/CCCC(O)=O MYHXHCUNDDAEOZ-FOSBLDSVSA-N 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- ZLQMRLSBXKQKMG-UHFFFAOYSA-N rauniticine Natural products COC(=O)C1=CC2CC3N(CCc4c3[nH]c5ccccc45)CC2C(C)O1 ZLQMRLSBXKQKMG-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- PFGWGEPQIUAZME-NXSMLHPHSA-N saralasin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 PFGWGEPQIUAZME-NXSMLHPHSA-N 0.000 description 1
- 229960004785 saralasin Drugs 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- CRPCXAMJWCDHFM-UHFFFAOYSA-M sodium;5-oxopyrrolidine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1CCC(=O)N1 CRPCXAMJWCDHFM-UHFFFAOYSA-M 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960003967 suloctidil Drugs 0.000 description 1
- 230000008833 sun damage Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- 229960003818 thymoxamine hydrochloride Drugs 0.000 description 1
- 229940035742 trimethaphan Drugs 0.000 description 1
- CHQOEHPMXSHGCL-UHFFFAOYSA-N trimethaphan Chemical compound C12C[S+]3CCCC3C2N(CC=2C=CC=CC=2)C(=O)N1CC1=CC=CC=C1 CHQOEHPMXSHGCL-UHFFFAOYSA-N 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/295—Iron group metal compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/62—Nymphaeaceae (Water-lily family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/734—Crataegus (hawthorn)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8969—Polygonatum (Solomon's seal)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
Definitions
- the invention relates to compositions and methods for treating skin disorders.
- Rosacea is a hereditary, chronic skin disorder that causes slight to severe redness and is often characterized by flare-ups and remissions. Rosacea primarily affects facial blood vessels. Rosacea is more frequently diagnosed in women, but tends to be more severe in men. The disorder typically begins after age 30 as a flushing or redness on the cheeks, nose, chin or forehead that may come and go. Over time, the redness tends to become ruddier and more persistent, and visible blood vessels may appear. In severe cases, rosacea skin can become inflamed and erupted. The affected skin tissue may swell and thicken, becoming sensitive to touch.
- vascular abnormalities are central to all stages and symptoms of rosacea.
- the blood vessels become hyper-responsive to internal and external stimuli including sun exposure, alcohol, medications, stress, emotions and aging of the skin. This hyper-responsiveness results in increased blood flow through the facial skin.
- One or all three of the following functional changes may take place in blood vessels affected by rosacea: dilation in response to a substance that normal blood vessels do not respond to, over- dilation, or dilation for an abnormally extended period of time.
- affected blood vessels may undergo extensive structural changes.
- Such structural changes may include: a) Permanent dilation of blood vessels (telangiectasia): Clinical studies on rosacea sufferers demonstrate that a significant portion of facial blood vessels are 'broken'; these vessels are permanently fixed in a dilated state. b) Damage to vascular smooth muscle: In rosacea sufferers, the muscular layer of facial blood vessels is often found to be damaged and abnormally thin. c) Damage to endothelial cells: In rosacea sufferers, the inner layer of the blood vessel wall is often found to be severely damaged and dysfunctional. d) Growth of new vessels: abnormal growth of new blood vessels may occur in rosacea sufferers. e) Orientation of blood vessels closer to the surface of facial skin: medical reports on rosacea sufferers indicate that blood vessels may become oriented so that they are closer to the surface of the facial skin. f) Abnormal fusion of blood vessels.
- the functional changes usually occur first, causing the flushing and ruddiness. Over time, this functional hyper-responsiveness may lead to increased blood vessel damage and subsequent structural changes. This results in more blood flow through the facial skin — causing more inflammation and damage — making rosacea a chronic and progressive disease.
- a method for treating an affected skin region of a patient having a skin disorder including a) applying a vasodilation composition to an affected skin region of a patient, the affected skin region exhibiting a skin disorder characterized by at least one abnormal blood vessel, and b) disrupting the tissue architecture of the at least one abnormal blood vessel.
- Vasodilation is applied to the affected skin region for a time sufficient to induce vasodilation of the at least one abnormal blood vessel in the affected skin region.
- abnormal blood vessel is understood to mean a blood vessel that exhibits one or more of the following functional and/or structural characteristics:
- blood vessels which are hyper-responsive to internal and external stimuli, e.g., sun exposure, alcohol, medication, stress, emotion, or aging of the skin, resulting in in increased blood flow through the skin;
- Skin disorders characterized by at least one abnormal blood vessel include without limitation vascular legions, rosacea, telangiectasia, spider veins, varicose veins, actinically damaged skin, venous hypertension, Poikiloderma vasculare atrophicans, vascular malformations, and hemangioma.
- Such skin disorders occur in patients who are, e.g., human patients.
- the patient is a non-human mammal, e.g., a dog, cat, horse or other mammal, or when the patient is a bird, the various embodiments of the invention are useful as veterinary methods of treatment.
- vasodilation refers to the dilation, e.g., by widening or by other means, of blood vessels.
- Vasodilators useful in the various embodiments of the invention include, e.g., arginine, preferably L-arginine.
- Other useful vasodilators include tolazoline, methyl nicotinate, and nitroprusside.
- a vasodilation composition may be formulated to include arginine HCl, urea, glycerin, hydroxyethylcellulose, allantoin, and methylisothiazolinone.
- the vasodilation composition can include arginine, preferably L-arginine, in the range of 0.001% to 10.0% w/w, e.g., 0.01% to 10.0% w/w.
- the method can include allowing a wait time sufficient for the vasodilation composition to cause dilation of the affected, i.e., abnormal, blood vessels prior to introducing the energy, such time referred to herein as a "vasodilation time".
- non-invasively disrupting the tissue architecture of the at least one abnormal blood vessel includes disruption of interactions between endothelial cells in the walls of the blood vessel.
- disruption of endothelial interactions can lead to collapse of the blood vessel.
- disruption of endothelial interactions can further lead to ischemia of the blood vessel.
- disrupting the tissue architecture of the at least one abnormal blood vessel e.g., by disrupting endothelial cell interactions, can lead to re-orientation or re-arrangement of abnormal blood vessels.
- non-invasive is meant a procedure that is performed on a blood vessel without exposing the blood vessel surgically, and without the device used to perform the procedure, e.g., a device that heats, compresses, or rearranges the blood vessel tissue, directly contacting the blood vessel tissue.
- a device can be used that delivers energy to the vessel through surrounding tissue, without touching the vessel itself.
- the tissue architecture of the at least one abnormal blood vessel can be disrupted by selectively heating the abnormal blood vessels by raising the temperature of the abnormal blood vessels relative to the temperature of surrounding tissue.
- the process of disrupting the tissue architecture of the abnormal blood vessels is frequently referred to herein as the "treatment” step. It can be accomplished by, without limitation, introducing energy to the abnormal blood vessels, e.g., by exposing the affected skin region to electromagnetic radiation, such as by photothermolysis, or to ultrasound and/or radio frequency radiation. Additional methods of non-invasive induction of disruption of abnormal blood vessel tissue architecture are known to those skilled in the art.
- non-invasively inducing ischemia includes administering a non-invasive treatment which selectively heats a target blood vessel to cause ischemia (or, in the case of already ischemic blood vessels, to increase ischemia), followed by cell death and degradation.
- a non-invasive method of inducing ischemia is to apply an external energy source that is capable of delivering energy in a wavelength preferentially absorbed by a blood vessel, as opposed to surrounding tissues, thereby selectively heating and thermo-damaging the walls of the blood vessel relative to the surrounding tissue.
- the invention After disrupting the tissue architecture of abnormal blood vessels, it is advantageous for the invention to optionally include applying a vasoconstriction composition to the affected skin region so as to cause vasoconstriction of the at least one blood vessel.
- vasoconstriction refers to constriction, e.g., narrowing, of blood vessels.
- Vasoconstrictors useful in the various embodiments of the invention include, e.g., phytonin.
- Other useful vasoconstrictors include phenyl epinephrine, caffeine, butcher's bloom extract, and bugleweed extract.
- vasoconstrictor formulation includes phytonin, aloe vera juice, arnica extract, cypress extract, Solomon's seal extract, a glyceryl stearate and peg- 100 stearate, sodium palmitoyl proline, nymphaea alba flower extract, cyclomethicone, stearic acid, glycerin, cetyl alcohol, butcher's broom extract, bugleweed extract, triethanolamine, pomegranate oil, allantoin, methylisothiazolinone, grapefruit oil, and an alkyl acrylate crosspolymer.
- kits which is supplied to a patient, or to a health care provider or cosmetologist treating a patient.
- the kit can include, without limitation, a first topical skin formulation including a vasodilation composition, and a second topical skin formulation including a vasoconstriction composition.
- the kit can include written instructions for use, by or on a patient, of the first topical skin formulation prior to receipt by the patient of a treatment that non-invasively disrupts tissue architecture of an abnormal blood vessel, e.g., by a non-invasive ischemia-inducing treatment, and of the second topical skin formulation after receipt by the patient of a treatment that non-invasively disrupts tissue architecture of an abnormal blood vessel, e.g., by a non-invasive ischemia-inducing treatment.
- Other components can optionally be added to the kit, such as topical compositions to be applied while treating to disrupt tissue architecture, e.g., inducing ischemia, such as, e.g., a pain medication in a topical formulation.
- Methods of the invention enhance treatment, e.g., thermolysis treatment, for various vascular skin disorders, by increasing the number and size of targeted blood vessels, optionally encouraging degradation and absorption of the necrotic tissue, and promoting healing.
- the embodiments of the invention provide numerous advantages. For example, applying the pre-treatment vasodilator to the skin increases the number of blood vessels that the treatment is able to target. Small blood vessels that would not contain enough blood to be photothermolysis targets without the enhanced flow induced by the pre-treatment vasodilator would otherwise be missed by the energy source. Thus, embodiments of the invention can prevent tiny abnormal blood vessels from becoming large abnormal vessels that will require further treatment.
- Another advantage of applying a vasodilator to the skin prior to treatment to disrupt blood vessel tissue architecture, e.g., induce ischemia, e.g., with an energy source, is increased blood flow to blood vessels.
- Blood is the selective target for the energy source, so this results in larger cross sectional areas to be targeted within a blood vessel and more energy to be focused within that area to enhance ischemia of the blood vessel.
- vasodilator to the skin prior to treating to disrupt blood vessel tissue architecture, e.g., induce ischemia, is that vasodilatation of the blood vessels causes the endothelial wall of the blood vessel to stretch and decrease in thickness. Thinner blood vessels are more easily damaged by the photothermolysis process than normal vessels, enhancing the effect of photothermolysis and increasing ischemia.
- vasoconstrictors enhance the degradation of the ischemic blood vessel causing the vessels to shrink and collapse.
- vasoconstrictors enhance the degradation of the ischemic blood vessel causing the vessels to shrink and collapse.
- Further advantages of applying a post treatment vasoconstrictor are that (1) anti-inflammatory agents in the formulation promote healing; and (2) the formulation contains skin-soothing agents that help to alleviate the sometimes painful effects of the process of inducing ischemia, such as by energy treatment.
- An advantage of some embodiments of the present invention is that the number of treatment sessions, e.g., photothermolysis treatment sessions, needed is reduced compared to energy treatment carried out in the absence of the application of a pre-treatment vasodilator, resulting in decreased treatment costs for patients, fewer visits to the doctor's office by patients, and greater numbers of patients that can be treated by each doctors.
- the methods of the various embodiments of the invention are simple, noninvasive, more effective than prior methods, and enhance the results of each treatment to induce ischemia. Such methods are safe and effective.
- the topical formulations are easy to apply and glide easily over the skin.
- Fig. 1 is a flow diagram illustrating a method in accordance with an embodiment of the present invention.
- FIG. 2 is a flow diagram illustrating a method in accordance with another embodiment of the present invention.
- Fig. 3 is a chart showing the results of a clinical trial of an embodiment of the invention.
- Embodiments of the present invention relate to compositions and methods for treatment of skin disorders.
- the compositions and methods are used for the treatment of rosacea, and for the treatment of skin disorders involving vascular lesions.
- Embodiments of the invention can also be used in the treatment of spider veins, varicose veins, actinically damaged skin, venous hypertension, Poikiloderma vasculare atrophicans, vascular malformations, hemangioma and telangiectasia.
- topically applied vasodilator agents increase the blood flow to a targeted area prior to treatment.
- a targeted energy source then induces ischemia of blood vessels in the area.
- a subsequent topical application of a vasoconstrictor or antiinflammatory composition can then be applied to promote healing or ameliorate discomfort.
- a composition of an embodiment of the invention can be a topical formulation, to be applied topically to the region of skin to be treated.
- a vasodilation composition or a vasoconstrictor composition can be in any delivery form known to those of ordinary skill in the art as appropriate for application to the skin, including a cream, lotion, ointment, foam, or gel.
- a composition of the invention can be applied by a patch.
- Fig. 1 shows a flow chart in accordance with an embodiment of the invention.
- a patient with rosacea or other disorder characterized by one or more abnormal blood vessels is selected as a suitable candidate for treatment (step 100).
- a vasodilator is applied (e.g., rubbed into) to an affected skin region of the patient (step 110).
- the vasodilator may be a topically applied composition which contains an active ingredient that causes vasodilatation of a blood vessel.
- a vasodilation time is allowed for the blood vessel or vessels to become dilated (e.g., 5 to 10 minutes).
- This vasodilation time can be a fixed amount of time, or sufficient time can be allowed, e.g., while the patient is being monitored, for indications that the blood vessels have dilated, prior to proceeding to the treatment step of inducing ischemia, e.g., by introducing energy.
- the vasodilator active ingredient in the vasodilation composition can be L-arginine, which may be included in a concentration range of 0.001% to 10%, e.g., .01% to 10.0% w/w, with the balance made of inactive ingredients or other active ingredients.
- the vasodilation composition can include other active vasodilation ingredients known to those of ordinary skill in the art.
- vasodilating agents include ginger extract, ginkgo biloba, hawthorne extract, bamethan sulphate, bencyclane fumarate, benpurodil hemisuccinate, benzyl nicotinate, buflomedil hydrochloride, buphenine hydrochloride, butalamine hydrochloride, cetledil citrate, ciclonicate, cinepazide maleate, cyclandelate, di-isopropylammonium dichloroacetate, ethyl nicotinate, hepronicate, hexyl nicotinate, Ifenprodil tartrate, inositol nicotinate, isoxsuprine hydrochloride, kallidinogenase, methyl nicotinate,
- vasodilators include nitroglycerin, labetalol, thrazide, isosorbide dinitrate, pentaerythritol tetranitrate, digitalis, hydralazine, diazoxide and sodium nitroprusside, in a concentration range of 0.001 to 10.0% w/w, e.g., 0.01% to 10.0% w/w.
- the vasodilation composition can be administered in a formulation that further includes substances that improve penetration or bioavailability of the active vasodilation ingredients.
- the vasodilation composition can include a combination of phospholipids, fatty acids, chemical penetration enhancers and binding components that result in enhanced diffusion of the active ingredient into and through the stratum corneum.
- the non-active ingredients of the vasodilation formulation can be selected from those known in the art, including distilled water, urea, propylene glycol, acrylates/c 10-30 alkyl acrylate crosspolymer, allantoin, DMDM hydantoin, methylparaben, and excipients known to those skilled in the art as useful for formulating pharmaceutical preparations in a concentration range of 0.001% to 10.0% w/w., e.g., 0.01% to 10.0% w/w.
- the energy is introduced into the dilated blood vessels (step 120).
- the energy can be in the form of electromagnetic radiation, such as pulsed and non-pulsed laser light or non-coherent light, e.g., at a wavelength range of 30 to 1100 nanometers, or, e.g., a wavelength of 500 to 1100 nanometers.
- One process of using light energy to induce selective heating and ischemia is known in the art as photothermolysis, where light energy is absorbed by chromophores in hemoglobin and oxyhemoglobin and is converted to heat. This selective heating increases the temperature in the red blood cells in the endothelium of the blood vessel wall causing ischemia, cell death and re-absorption of the blood vessel by the body.
- energy can be introduced in the form of ultrasound or in the form of radio-frequency electromagnetic radiation.
- the applied energy is introduced with the objective of inducing ischemia of one or more blood vessels in the affected skin region.
- energy is supplied in the form of visible light that is preferentially absorbed by the blood vessel or its contents.
- the light can be of a wavelength that is preferentially absorbed by hemoglobin carried in the blood vessels. The light energy absorbed by the hemoglobin is converted to thermal energy, thereby raising the local temperature and causing ischemia, cell death and eventual re-absorption of the blood vessel by the body.
- the source of the light can be a pulsed dye laser, diode laser, Er: YAG laser, Nd:YAG laser, xenon flash lamp, alexandrite laser, semiconductor diode, copper vapor laser, argon ion laser, krypton ion laser, or other suitable light and/or laser source known to those skilled in the art.
- vasodilator before irradiation, a larger number of blood cells may be present in the blood vessel, thereby increasing the efficiency of treatment. Additionally, the vasodilation step may make the application of energy more efficient with regard to induction of ischemia due to thinning of the vessel walls. Vasodilation may also increase the ability of the applied energy to target smaller vessels that might otherwise evade treatment. If left untreated, the smaller vessels would cause unwanted future pathologies, requiring further treatment and additional expense.
- Fig. 2 shows a flow chart in accordance with another embodiment of the invention.
- a vasoconstrictor is applied (step 130).
- the vasoconstrictor may be applied as a topical formulation.
- the application of the vasoconstrictor can confer one or more of the benefits of enhancing degradation of ischemic blood vessels, promoting healing, and alleviating pain.
- the vasoconstrictor formulation may also include anti-inflammatory, anti-edemic, analgesic, or other substances known in the art to promote healing or to enhance patient comfort.
- the vasoconstrictor composition formulation can include phytonin.
- phytonin is present in a vasoconstrictor formulation within a concentration range of 0.001% to 10.0% w/w., e.g., 0.01% to 10.0% w/w.
- the vasoconstriction composition can include other active vasoconstriction ingredients known to those of ordinary skill in the art.
- vasoconstricting agents include phenyl-epinephrine and caffeine.
- Additional examples of vasoconstricting agents include arnica extract, cypress extract, Solomon's seal extract, nymphaea alba flower extract, butcher's broom extract, grapefruit oil, pomegranate and bugleweed extract, in a concentration range of 0.001% to 10.0% w/w., e.g., 0.01% to 10.0% w/w.
- the vasoconstrictor formulation can also include one or more inactive ingredients, such as aloe vera juice, distilled water, cetyl alcohol, glyceryl stearate/PEG-100 stearate, sodium palmitoyl proline, sodium PCA, cyclopentasiloxane, dimethicone crosspolymer and other excipients known to those skilled in the art for use in formulating pharmaceutical preparations.
- inactive ingredients such as aloe vera juice, distilled water, cetyl alcohol, glyceryl stearate/PEG-100 stearate, sodium palmitoyl proline, sodium PCA, cyclopentasiloxane, dimethicone crosspolymer and other excipients known to those skilled in the art for use in formulating pharmaceutical preparations.
- the vasoconstrictor formulation can further include substances to improve penetration or bioavailability of the active vasoconstrictor ingredients.
- the formulation may include one or a combination of phospholipids, fatty acids, chemical penetration enhancers, and binding components that result in enhanced diffusion of the active ingredient into and through the stratum corneum. Substances which improve the penetration or bioavailability of active ingredients in topical formulations are known to those of ordinary skill in the art.
- steps 110 and 120 may be repeated for a given number of cycles prior to applying vasoconstrictor (step 130).
- the vasoconstrictor formulation can be re-applied after the process of Fig. 1 or Fig. 2 is complete to help maintain the benefits of the treatment.
- a healthcare provider may instruct a patient to apply a vasoconstrictor composition on a periodic basis after treatment (e.g., one or more times daily).
- the vasoconstrictor formulation used subsequent to the first application of step 130 can be the same formulation as used in vasoconstriction treatment step 130, or can be one or more of the different vasoconstrictor formulation embodiments described above.
- Example 1 A clinical study was undertaken in order to demonstrate the effectiveness of the method of Fig. 2 in improving the outcome of laser/photo facial treatments. In the study, 16 patients with moderate facial redness served as their own test subject and control.
- VISIATM Complexion Analysis System Canfield Scientific, Fairfield NJ.
- the VISIATM system has the ability to visualize skin conditions related to abnormal melanin concentrations or vascular disorders. Visualized abnormalities include conditions such as sun damage, rosacea, melasma, telangiectasia and others.
- the vasodilator composition contained water, arginine HCl, urea, glycerin, hydroxyethylcellulose, allantoin, methylisothiazolinone.
- the percentage of each reagent in the vasodilation composition is shown in Table 1 on a weight/weight basis. This vasodilation composition had a pH of 5.1.
- Table 1 Table 1 :
- a layer of pre-energy treatment vasodilating composition was applied to the left side of the face and gently massaged into the skin. No pre-treatment composition was applied to the right side.
- each patient was treated with either a broad-band light source centered at 560 nm or a Nd Yag Laser at 1064 nm on both sides of the face. Treatments generally lasted for 15 minutes. The irradiation energy varied from 13 to 160 Joules.
- the wavelength of the irradiation was determined by a variety of factors, including the type of flushing the patient experiences, the individual's tolerance for pain and the patient's response to the treatment. For example, if the patient had discrete veins that could be traced for treatment, the 1064 wavelength was used since that is a pinpoint laser used for tracing vessels. If the patient had more flushing than discrete vessels, the skin was irradiated with pulsed light at 560 nm because this treatment is believed to be more effective toward flushing.
- the energy selected for the treatment was selected based on patient tolerance and wavelength, with patient pain tolerance being the primary factor .
- the energy goal was 14- 16 Joules for the 560 initial treatment. When using the 1064 wavelength, the starting point was generally 160 Joules. If the patient tolerated the higher wavelengths well and the practitioner believed that the treatment was not providing an ideal response, the energy level was increased. Often patient discomfort prevents treating at higher energy level without topical anesthetic.
- Energy treatments for each patient are set forth in Table 2. Table 2:
- the vasoconstrictor composition used in the example clinical trial contained phytonin, aloe vera juice, arnica extract, cypress extract, Solomon's seal extract, glyceryl stearate and peg- 100 stearate, sodium palmitoyl pro line, nymphaea alba flower extract, cyclomethicone, stearic acid, glycerin, cetyl alcohol, butcher's broom extract, bugleweed extract, triethanolamine, pomegranate oil, allantoin, methylisothiazolinone, grapefruit oil, acrylates/c 10-30 alkyl acrylate crosspolymer. As detailed in Table 3, below, the composition was formulated from four parts and had a pH of 6.5. The percentage of each reagent in the vasoconstriction composition is shown in Table 3 on a weight/weight basis. Table 3:
- Fig. 3 is a chart showing the results of a clinical trial of an embodiment of the invention, each column to be understood as (1) patient number; (2) the date of VISIATM measurement prior to treatment; (3) the date of treatment; (4) the date of VISIATM measurement after treatment; (5) number of reds in treated (left) area before treatment; (6) number of reds in treated (left) area after treatment; (7) percent change in number of reds in treated (left) area before versus after treatment; (8) evaluation of improvement in treated (left) area by VISIATM; (9) evaluation of improvement in treated (left) area by photograph; (10) number of reds in untreated (right) area before treatment; (11) number of reds in untreated (right) area after treatment; (12) percent change in number of reds in untreated (right) area before versus after treatment; (13) evaluation of improvement in untreated (right) area by VISIATM; (14) evaluation of improvement in untreated (right) area by photograph; and (15) evaluation of treated versus untreated areas.
- “Number of reds” refer
- the outcome of the clinical study demonstrates the effectiveness of the vasodilating and vasoconstricting compositions described herein as agents to improve the outcome of laser treatments for reducing facial redness. This may result in a reduction in rosacea symptoms and an increase in patient satisfaction.
- Example 2 The compositions of the invention can be supplied in the form of a kit.
- the kit can be supplied to a patient, or to a health care provider or cosmetologist treating a patient.
- the kit can include, without limitation, a first topical skin formulation including a vasodilation composition, and a second topical skin formulation including a vasoconstriction composition.
- the kit can include written instructions for use, by or on a patient, of the first topical skin formulation prior to receipt by the patient of an ischemia-inducing treatment and of the second topical skin formulation after receipt by the patient of an ischemia-inducing treatment.
- kits can optionally be added to the kit, such as topical compositions to be applied while inducing ischemia, such as, e.g., a pain medication in a topical formulation.
- Vasodilation compositions and vasoconstriction compositions useful in such a kit are prepared according to the methods set forth above, and are preferably supplied in the kit in an amount suitable for a single regimen.
- the kit can further include a energy source device, e.g., a laser, a high-intensity light, or an ultrasound transducer.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Radiology & Medical Imaging (AREA)
- Emergency Medicine (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Anesthesiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Dans un procédé de traitement d’une région cutanée affectée d’un patient souffrant d’un trouble cutané, il est appliqué une composition vasodilatatrice sur une région cutanée affectée d’un patient, la région cutanée affectée présentant un trouble cutané caractérisé par au moins un vaisseau sanguin anormal. La région cutanée affectée est ensuite traitée de manière à perturber de manière non invasive l’architecture tissulaire, par exemple, par l’induction d’une ischémie, d’au moins un vaisseau sanguin anormal. Il est alors possible d’appliquer une composition vasoconstrictrice sur la région cutanée afin de provoquer une vasoconstriction d’au moins un vaisseau sanguin pour favoriser la cicatrisation.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09763660A EP2307001A1 (fr) | 2008-06-11 | 2009-06-11 | Contrôle de la physiologie des vaisseaux sanguins pour le traitement de troubles cutanés |
CA2727710A CA2727710C (fr) | 2008-06-11 | 2009-06-11 | Controle de la physiologie des vaisseaux sanguins pour le traitement de troubles cutanes |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US6054308P | 2008-06-11 | 2008-06-11 | |
US61/060,543 | 2008-06-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009152372A1 true WO2009152372A1 (fr) | 2009-12-17 |
Family
ID=40910864
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2009/047098 WO2009152372A1 (fr) | 2008-06-11 | 2009-06-11 | Contrôle de la physiologie des vaisseaux sanguins pour le traitement de troubles cutanés |
Country Status (4)
Country | Link |
---|---|
US (3) | US8367122B2 (fr) |
EP (1) | EP2307001A1 (fr) |
CA (1) | CA2727710C (fr) |
WO (1) | WO2009152372A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104524189A (zh) * | 2014-12-30 | 2015-04-22 | 兰州古驰生物科技有限公司 | 一种用于调理干性皮肤的中药保健制剂 |
CN108126006A (zh) * | 2016-12-01 | 2018-06-08 | 林凡友 | 断血流口服制剂的制备工艺 |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010034019A1 (fr) | 2008-09-22 | 2010-03-25 | Biochemics, Inc. | Administration transdermique de médicaments employant un osmolyte et un agent vasoactif |
EP2352543B1 (fr) * | 2008-12-04 | 2019-04-03 | BioChemics, Inc. | Procédés et compositions pour un retrait de tatouage |
EP2637634B1 (fr) | 2010-11-12 | 2017-05-17 | Colgate-Palmolive Company | Produit d'hygiène orale, procede d'utilisation et de fabrication de celui-ci |
US9579355B1 (en) * | 2012-10-05 | 2017-02-28 | Clark Pharmaceuticals LLC | Composition and method of treating actinic purpura |
EP2978412A2 (fr) * | 2013-03-25 | 2016-02-03 | Sloan Kettering Institute For Cancer Research | Articles et procédés pour prévenir et traiter des événements indésirables dermatologiques |
EP3019238A4 (fr) * | 2013-07-10 | 2017-03-29 | Oxys AG | Dispositifs et méthodes de distribution d'énergie thérapeutique |
TWI626168B (zh) * | 2013-07-25 | 2018-06-11 | 滿捷特科技公司 | 噴墨列印及保持噴嘴水合作用的方法 |
US20150065943A1 (en) * | 2013-08-27 | 2015-03-05 | Matthew DeBow | Method to Accelerate Healing |
WO2020069013A1 (fr) | 2018-09-27 | 2020-04-02 | BioPhysics Pharma, Inc. | Système d'administration transdermique de médicament |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001017498A1 (fr) * | 1999-09-09 | 2001-03-15 | Pentapharm Ltd. | Utilisation d'acide linoleique conjugue pour le traitement topique de la cellulite |
US6306130B1 (en) | 1998-04-07 | 2001-10-23 | The General Hospital Corporation | Apparatus and methods for removing blood vessels |
US6486206B1 (en) * | 1997-09-29 | 2002-11-26 | Cprx Inc. | Mechanical and pharmacologic therapies to treat cardiac arrest |
WO2005123190A1 (fr) * | 2004-06-18 | 2005-12-29 | Smith & Nephew, Plc | Traitement par ultrasons des affections ou troubles cutanes et du cancer, et regeneration musculaire/osseuse |
EP1621192A1 (fr) * | 2004-07-16 | 2006-02-01 | BioChemics, Inc. | Système thérapeutique transdermique contenant une quantité optimisée de vasodilatateur |
US20060217690A1 (en) | 2005-03-22 | 2006-09-28 | Bastin Norman J | Method for treating various dermatological and muscular conditions using electromagnetic radiation |
WO2007086395A1 (fr) * | 2006-01-24 | 2007-08-02 | Hamamatsu Foundation For Science And Technology Promotion | Nécessaire de thérapie photodynamique |
WO2008054059A1 (fr) * | 2006-10-31 | 2008-05-08 | Amorepacific Corporation | Utilisation d'une composition pour traiter l'obésité et le diabète |
WO2008109124A1 (fr) * | 2007-03-06 | 2008-09-12 | Novalar Pharmaceuticals, Inc. | Utilisation de nitroglycérine pour anesthésie locale inverse |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4440777A (en) * | 1981-07-07 | 1984-04-03 | Merck & Co., Inc. | Use of eucalyptol for enhancing skin permeation of bio-affecting agents |
US4933184A (en) * | 1983-12-22 | 1990-06-12 | American Home Products Corp. (Del) | Menthol enhancement of transdermal drug delivery |
US4857328A (en) * | 1986-09-29 | 1989-08-15 | Tecma Laboratories, Inc. | Skin therapeutic mixture containing aloe vera extract |
US5229130A (en) * | 1991-12-20 | 1993-07-20 | Cygnus Therapeutics Systems | Vegetable oil-based skin permeation enhancer compositions, and associated methods and systems |
DE4201172C1 (en) * | 1992-01-17 | 1993-07-22 | Alfatec-Pharma Gmbh, 6900 Heidelberg, De | Pellets contg. Aloe vera extract - useful, e.g. as antiinflammatory of antibiotic agents, or for treating gastric ulcers |
US5460821A (en) * | 1993-06-23 | 1995-10-24 | Masiz; John J. | Molecular transdermal transport system |
US5853751A (en) * | 1993-06-23 | 1998-12-29 | Masiz; John J. | Molecular transdermal transport system |
US5645854A (en) * | 1993-06-23 | 1997-07-08 | Masiz; John J. | Molecular transdermal transport system |
FR2732221B1 (fr) * | 1995-03-28 | 1997-04-25 | Oreal | Utilisation d'un antagoniste de cgrp pour traiter les rougeurs cutanees d'origine neurogene et composition obtenue |
CA2154979A1 (fr) * | 1995-07-28 | 1997-01-29 | Kenneth T. Armstrong | Preparation topique a base de phenylephrine |
FR2741262B1 (fr) * | 1995-11-20 | 1999-03-05 | Oreal | Utilisation d'un antagoniste de tnf-alpha pour le traitement des rougeurs cutanees d'origine neurogene |
US5895658A (en) * | 1997-09-17 | 1999-04-20 | Fossel; Eric T. | Topical delivery of L-arginine to cause tissue warming |
US6207713B1 (en) * | 1997-09-17 | 2001-03-27 | Eric T. Fossel | Topical and oral delivery of arginine to cause beneficial effects |
US5922332A (en) * | 1997-09-17 | 1999-07-13 | Fossel; Eric T. | Topical delivery of arginine to overcome pain |
US5902593A (en) * | 1997-10-01 | 1999-05-11 | Kent; Frances B. | Topically applied personal lubricant containing benzalkonium chloride as the active ingredient |
US7105172B1 (en) * | 1999-11-18 | 2006-09-12 | Bolla John D | Treatment of rosacea |
FR2808191B1 (fr) * | 2000-04-28 | 2004-03-05 | Oreal | Extrait de vegetal de l'espece olea europaea comme inhibiteur de no-synthase et utilisations |
US6635274B1 (en) * | 2000-10-27 | 2003-10-21 | Biochemics, Inc. | Solution-based transdermal drug delivery system |
BR0115474A (pt) * | 2000-11-17 | 2006-01-31 | Idenix Cayman Ltd | Composição e método para inibição da transmissão de hiv que usam 6-benzil-4-oxopirimidinas substituìdas aplicada por via tópica |
US20030091659A1 (en) * | 2001-11-09 | 2003-05-15 | Avon Products, Inc. | Topical composition having undifferentiated plant seed cells and method for using same |
US20030104043A1 (en) * | 2001-12-03 | 2003-06-05 | Brown Beverly Ann | Topical cream for alleviating spider veins |
US20050271596A1 (en) * | 2002-10-25 | 2005-12-08 | Foamix Ltd. | Vasoactive kit and composition and uses thereof |
US20040191278A1 (en) * | 2003-03-31 | 2004-09-30 | Christensen Flemming Kjaergaar | Topical agent for application to the skin prior to luminous treatment |
US6927206B2 (en) * | 2003-06-06 | 2005-08-09 | Procyte Corporation | Compositions and methods for treatment of rosacea |
JP2007532697A (ja) * | 2004-04-19 | 2007-11-15 | ストラテジック サイエンス アンド テクノロジーズ, エルエルシー | 局所的血流増大の有益な効果 |
US20050256204A1 (en) * | 2004-05-11 | 2005-11-17 | Bitter Patrick H Sr | Topical phenyl-epinephrine Rosacea treatment |
US20050287131A1 (en) * | 2004-06-25 | 2005-12-29 | Schock Joel F | Health supplement |
US7288263B2 (en) * | 2004-09-13 | 2007-10-30 | Evera Laboratories, Llc | Compositions and methods for treatment of skin discoloration |
US7566464B2 (en) * | 2005-09-01 | 2009-07-28 | Belfer William A | Cosmetic composition to accelerate repair of functional wrinkles |
CA2645073A1 (fr) * | 2006-03-08 | 2007-09-13 | Nuviance, Inc. | Composition de medicament a liberation transdermique et compositions topiques pour application cutanee |
US8354116B2 (en) * | 2007-06-18 | 2013-01-15 | Biochemics, Inc. | Bifunctional synthetic molecules |
-
2009
- 2009-06-11 US US12/483,073 patent/US8367122B2/en active Active
- 2009-06-11 WO PCT/US2009/047098 patent/WO2009152372A1/fr active Application Filing
- 2009-06-11 EP EP09763660A patent/EP2307001A1/fr not_active Ceased
- 2009-06-11 CA CA2727710A patent/CA2727710C/fr not_active Expired - Fee Related
-
2013
- 2013-01-03 US US13/733,247 patent/US20130245538A1/en not_active Abandoned
-
2016
- 2016-04-28 US US15/140,801 patent/US20160235846A1/en not_active Abandoned
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6486206B1 (en) * | 1997-09-29 | 2002-11-26 | Cprx Inc. | Mechanical and pharmacologic therapies to treat cardiac arrest |
US6306130B1 (en) | 1998-04-07 | 2001-10-23 | The General Hospital Corporation | Apparatus and methods for removing blood vessels |
WO2001017498A1 (fr) * | 1999-09-09 | 2001-03-15 | Pentapharm Ltd. | Utilisation d'acide linoleique conjugue pour le traitement topique de la cellulite |
WO2005123190A1 (fr) * | 2004-06-18 | 2005-12-29 | Smith & Nephew, Plc | Traitement par ultrasons des affections ou troubles cutanes et du cancer, et regeneration musculaire/osseuse |
EP1621192A1 (fr) * | 2004-07-16 | 2006-02-01 | BioChemics, Inc. | Système thérapeutique transdermique contenant une quantité optimisée de vasodilatateur |
US20060217690A1 (en) | 2005-03-22 | 2006-09-28 | Bastin Norman J | Method for treating various dermatological and muscular conditions using electromagnetic radiation |
WO2007086395A1 (fr) * | 2006-01-24 | 2007-08-02 | Hamamatsu Foundation For Science And Technology Promotion | Nécessaire de thérapie photodynamique |
WO2008054059A1 (fr) * | 2006-10-31 | 2008-05-08 | Amorepacific Corporation | Utilisation d'une composition pour traiter l'obésité et le diabète |
WO2008109124A1 (fr) * | 2007-03-06 | 2008-09-12 | Novalar Pharmaceuticals, Inc. | Utilisation de nitroglycérine pour anesthésie locale inverse |
Non-Patent Citations (4)
Title |
---|
KAUTZ G ET AL: "Management of rosacea with intense pulsed light (IPL) systems and laser", MEDICAL LASER APPLICATION, ELSEVIER, NL, vol. 23, no. 2, 15 May 2008 (2008-05-15), pages 65 - 70, XP022765685, ISSN: 1615-1615, [retrieved on 20080314] * |
KAUTZ, G. ET AL.: "Medical Laser Application", 15 May 2008, ELSEVIER, article "Management of rosacea with intense pulsed light (IPL) systems and laser" |
MCGILL D J ET AL: "The effect of ambient temperature on capillary vascular malformations", BRITISH JOURNAL OF DERMATOLOGY, vol. 154, no. 5, May 2006 (2006-05-01), pages 896 - 903, XP002540293, ISSN: 0007-0963 * |
See also references of EP2307001A1 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104524189A (zh) * | 2014-12-30 | 2015-04-22 | 兰州古驰生物科技有限公司 | 一种用于调理干性皮肤的中药保健制剂 |
CN108126006A (zh) * | 2016-12-01 | 2018-06-08 | 林凡友 | 断血流口服制剂的制备工艺 |
Also Published As
Publication number | Publication date |
---|---|
CA2727710A1 (fr) | 2009-12-17 |
US20100003353A1 (en) | 2010-01-07 |
CA2727710C (fr) | 2016-11-01 |
US20160235846A1 (en) | 2016-08-18 |
US20130245538A1 (en) | 2013-09-19 |
US8367122B2 (en) | 2013-02-05 |
EP2307001A1 (fr) | 2011-04-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2727710C (fr) | Controle de la physiologie des vaisseaux sanguins pour le traitement de troubles cutanes | |
Kozarev et al. | Novel laser therapy in treatment of onychomycosis | |
Del Rosso | Advances in understanding and managing rosacea: part 2: the central role, evaluation, and medical management of diffuse and persistent facial erythema of rosacea | |
US10537536B2 (en) | Transdermal drug delivery using an osmolyte and vasoactive agent | |
Kimura et al. | Long‐pulsed 1064‐nm neodymium: yttrium–aluminum–garnet laser treatment for refractory warts on hands and feet | |
Lui et al. | Photodynamic therapy of nonmelanoma skin cancer with topical aminolevulinic acid: a clinical and histologic study | |
Carruthers et al. | Cryolipolysis and skin tightening | |
JP2011521948A (ja) | 皮膚の炎症および変色のための方法ならびに組成物 | |
Coiante et al. | Assessment of the efficacy of cryolipolysis on abdominal fat deposits: a prospective study | |
JP7454492B2 (ja) | 皮膚障害に対する光線力学的治療方法 | |
Kim et al. | Combination treatment using bipolar radiofrequency-based intense pulsed light, infrared light and diode laser enhanced clinical effectiveness and histological dermal remodeling in Asian photoaged skin | |
Barge et al. | Correlations between photoactivable porphyrins’ fluorescence, erythema and the pain induced by PDT on normal skin using ALA-derivatives | |
Goldman et al. | ALA/PDT in the treatment of actinic keratosis: spot versus confluent therapy | |
Petermann | Comparison of pre-and post-treatment pain scores of twenty one horses with laminitis treated with acupoint and topical low level impulse laser therapy | |
Sun et al. | Chemical peeling with a modified phenol formula for the treatment of facial freckles on asian skin | |
US20050256204A1 (en) | Topical phenyl-epinephrine Rosacea treatment | |
RU2811255C1 (ru) | Способ лечения конглобатного подтипа розацеа по точкам | |
Jiang et al. | Ultrapulsed CO2 Laser Combined with Long-pulsed Nd: YAG Laser for the Treatment of Oral and Maxillofacial Pyogenic Granuloma | |
RU2286791C1 (ru) | Способ лечения рубцов | |
RU2704782C1 (ru) | Способ криогенного лечения онихомикоза | |
RU2625293C1 (ru) | Способ лечения витилиго | |
US11903909B2 (en) | Combined liposuction method | |
JP2013542922A (ja) | 真菌感染症の処置 | |
Tenenbaum et al. | Cosmetic Dermatology | |
Saedi et al. | Injectable fat‐reducing therapies: fat reduction |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 09763660 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2727710 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2009763660 Country of ref document: EP |